Monday, January 7, 2013

While all of the varieties of Multiple Sclerosis are vile, especially troublesome are the progressive flavors of the disease. Over the last two decades, strides have been made in understanding and treating Relapsing Remitting MS, the most common form of the illness. While the available treatments for RRMS are far from universally effective, don’t address the still unknown root cause of the disease, and some carry with them downright frightening side effect profiles, they do significantly improve the quality of life for many of the patients taking them. No such strides have been made in the fight against progressive MS. Patients suffering from Secondary Progressive MS (SPMS) or Primary Progressive Multiple Sclerosis (PPMS) are left with few if any treatment options, and their care often amounts to nothing more than aggressive attempts at symptom management. The reasons for this are many, including the relatively small patient population, and the difficulty in designing cost-effective treatment trials with readily measurable endpoints.

Given the confusion regarding the subtypes of MS that I see on Internet forums, it seems that a quick rundown of the subtypes may be in order. Relapsing Remitting Multiple Sclerosis, RRMS, is marked by distinct disease relapses, during which a patient suffers a significant onset of symptoms, followed by periods of remission, when those symptoms subside and the patient returns to their former physical state, albeit sometimes with additional accumulated disability. After a period of years, the disease of many RRMS patients transitions into Secondary Progressive Multiple Sclerosis, SPMS, at which point they stop having relapses and remissions, and instead suffer a steady accumulation of symptoms. Primary Progressive Multiple Sclerosis, PPMS, is much like SPMS, in that patients experience a steady increase in symptoms and disability, without the peaks and valleys that signify RRMS. The difference between SPMS and PPMS is that, by definition, all SPMS patients must have had RRMS first, whereas PPMS patients experience progressive illness from the onset of their disease. If a patient has ever experienced relapses and remissions then they cannot have PPMS. If such patients find themselves, over time, suffering from a strictly progressive course of the disease, they would fall into the SPMS category. As mentioned above, both SPMS and PPMS, though distinct subtypes of the disease, unfortunately share the same lack of effective treatment options.

There is, though, one treatment, called intrathecal methotrexate, that has shown promise in limited real-world implementation when used to treat progressive MS, both in anecdotal patient reports and retrospective studies conducted by the one MS clinic that makes extensive use of the treatment. Unfortunately, most MS neurologists are unaware of the potential benefits of intrathecal methotrexate for progressive MS patients, and many who are aware of the protocol are often too dubious of the treatment to give it serious consideration.

The intrathecal methotrexate treatment protocol involves injecting the drug methotrexate directly into the spinal fluid of progressive MS patients, via a lumbar puncture. The treatment is typically given every eight weeks, using a very thin needle to inject the medication into the lumbar region of the spine. While many patients may be understandably queasy about the prospect of having a lumbar puncture every eight weeks, when done by experienced medical personnel the procedure should cause minimal discomfort with few side effects. When weighed against the insidious nature of progressive MS left untreated, periodic lumbar punctures, as unsavory a prospect they may be, certainly are preferable to an inexorable slide towards significant disability.

Used extensively by the International Multiple Sclerosis Treatment Center of New York (where I am a patient), the use of intrathecal methotrexate has been shown to be widely effective in limited studies published by the clinic’s researchers and practicing physicians, led by Dr. Saud Sadiq. In one such study of 121 patients, disability scores were found to be stable or improved in 89% of SPMS patients and 82% of PPMS patients one year after their last treatment (click here). A longer-term study (click here) found that 48% of patients experienced no increase in disability after treatment periods ranging from 3 to 6 years. As noted, both studies looked at small patient populations, and did not include a placebo group for comparison, but their findings do offer some intriguing evidence of the efficacy of this treatment in a notoriously hard to treat group of patients. It is thought that intrathecal methotrexate, which has known anti-inflammatory properties, also may inhibit the progression of MS by interacting with astrocytes, cells that are associated with the formation of MS lesions (click here).

When given orally or intravenously, methotrexate’s side effects are typical of many chemotherapy drugs, and include hair loss and nausea. In the tiny doses used in intrathecal injections, though, the side effects are negligible. I experienced absolutely no side effects from the treatment, and neither has any patient I’ve met have has also undergone the protocol.

In my time under Dr. Sadiq’s care (since 2004), I have tried the treatment on two occasions, totaling eight intrathecal injections of methotrexate. Unfortunately, the treatment did me no benefit, but I am a very poor example upon which to base any opinions, since my disease is highly atypical, if it is even MS at all (click here). Another popular MS blogger, my good friend Mitch, who writes the terrific MS blog “Enjoying the Ride”, suffers from classic PPMS, and recently happily announced that after five spinal injections of methotrexate, the progression of his disease has slowed to a trickle, and may have even stopped (click here for all of Mitch's methotrexate posts). As documented in his blog, Mitch had to do a bit of heavy lifting to get his neurologist to agree to treat him with intrathecal methotrexate, but he eventually got his neurologist to agree after providing him with research documentation linked to in the above paragraph. Mitch's experiences with the treatment haven't always been easy, but have been well worth it if indeed the progression of his illness has been beneficially impacted.

Why has the use of intrathecal methotrexate for the treatment of progressive MS not been studied more extensively? You’d think that a treatment as potentially effective as this would attract researchers and pharmaceutical companies like flies to honey. Unfortunately, the sad truth is that it all comes down to money. Methotrexate is a very old drug (click here), first developed in the 1950s to treat certain forms of leukemia. It has since been shown to be effective in treating other kinds of cancer, as well as lupus and a variety of other autoimmune diseases. It was granted FDA approval for use in treating rheumatoid arthritis in 1988. Because the drug is so old, any patents held on it have long since expired, and it’s available as a cheap generic compound. In the extremely small doses used to treat MS intrathecally, each shot costs about five dollars. Therefore, there is very little profit to be derived from marketing methotrexate, and so it receives no attention from the pharmaceutical companies, which at this point fund the vast majority of medical research conducted in the USA. Many other potentially effective treatments, such as low dose naltrexone (LDN), also fall into this same trap, left largely untested and unheralded simply because facilitating robust trials would not be cost-effective. Forget about patient well-being, the financial bottom line has become THE bottom line in medicine as it is now practiced, oftentimes to the detriment of the very people the system supposedly exists to benefit. When patients are viewed first as consumers, something is very wrong.

Based on what I know about this treatment, I’d suggest that any patient with progressive MS at least discuss intrathecal methotrexate with their MS neurologist. Be prepared for pushback. As noted previously, most neuros are reticent to try this approach. This is where the importance of patient education and self advocacy comes in. When talking to your doctor, bring back up materials, such as printouts of the research linked to in this post, and some of Mitch’s blog entries from Enjoying the Ride. With other treatment options limited if not nonexistent, and the long-term prognosis of those suffering from progressive multiple sclerosis so daunting, all options need to be put on the table.

Although having a chemotherapy drug injected directly into the spinal fluid may sound a bit radical, when broken down to its individual bits the protocol really isn’t all that scary. Methotrexate has been used safely and effectively for decades, and in the tiny doses used in this protocol presents very little risk. Lumbar punctures, while no joyride, are routine for most neurologists, and the use of very fine needles minimizes the chance of postprocedure complications. Many neurologists are willing to try the new generation of powerful immunosuppressant drugs now used to treat RRMS on their progressive patients, with no proof whatsoever of their efficacy in treating the progressive forms of MS. Given the potentially dire consequences of leaving progressive MS untreated, shouldn’t a potential therapy that has already helped hundreds of patients be given serious consideration, regardless of its "outside the box" designation?

On the day of my diagnosis, I vowed that if this disease was going to take me down, I was going to go down swinging, both fists battered and bloodied, all guns blazing. Progressive MS (or whatever it is that I’ve got) isn’t very likely to show much mercy, and as a guy who grew up on the streets of New York City I know that when faced with such an adversary, all bets are off. You do what you have to do, throw any rules right out the window, and meet fire with fire. Like it or not, this is mortal combat, and if getting a spike in the back every couple of months provides even the slightest chance of beating this thing back, I was, and am, willing to take it. Treatment with intrathecal methotrexate did not work for me, but it has worked for some, and that alone should give all engaged in the struggle reason enough to give it serious consideration. Talk to your doctor, and pay close attention to their advice, but always remember that in the fight against your disease, the doctor-patient relationship should not be a dictatorship, but a partnership. Treatment with intrathecal methotrexate may be unconventional, but, as it stands now, the conventional modality for treating progressive MS has been nothing but an abject failure. Hopefully, with ongoing research, this situation will turn, but in the meantime I say self educate, agitate, and take an active role in mapping the attack on your illness.

22 comments:

Thanks for the great explanation of what this stuff is, where it came from, and who is using it. Oddly, someone close to me is, at this very moment, considering which chemo treatment to select for an advanced cancer, and one of the options is something called MVAC. Each letter stands for a different drug and the M is Methotrexate.

I forwarded your post and your comments about your own fight meant a great deal to him. As we all know, attitude is everything but science isn't bad either.

I'm the one with MS but adversity makes strange alliances; it's not surprising how much his battle and mine have in common.

Thanks Marc :)One point I like to add when there is a discussion about disease types comes back to basic maths. If a person is dx-ed with RRMS then they are going to advance to SPMS, so what does that mean to the real or realistic stats that are produced on MS disease types.Is it not correct that once conversion to SPMS occurs the stats for RRMS need to be adjusted back accordingly!Another thought comes to mind regarding the treatments of Inflammation, it's one approach to want to stop the inflammation as a separate issue to the total disease and another very different approach to work on the cause of inflammation, such as an infection. Bacterial infection as a root cause of inflammation has been thrown around for decades in MS studies. Using the Western approach to medicine the attempts to 'stop' infection are generally a mono drug use and for a limited period of time. There are millions of bacteria in our systems, some are vital to life and some the opposite. If 'Science' has only named 0.04% of Bacteria then we are heading uphill in understanding the actions of the bacteria we posses.In Eastern Medicine practises the approach is a broad spectrum of natural products that we as Westerners have no idea how they work or the synergy that occurs when many natural herbs for instance are used to combat overloads of Bacteria.So I am of the opinion we need to consider when people such as yourself have an unknown and uncontrollable disease that a new Paradigm in approach is required. For me I have started on the Wheldon/Paul Thibault CPn protocol after having blood tests and self tests for CPn. The effects of the additional herbs I use and the side effects of the ABx causing photo-sensitivity and Vit D causing cellular Apoptosis retesting of infected cells tells me that the results of research and study may be confused by the synergy effects.Thanks Marc for another great read!Nigel

Marc, thanks for raising awareness of intrathecal methotrexate for progressive MS. As you mentioned, I have had some success with this treatment. I don't know how long it will last, but I am grateful for each day that I have slowed or even stopped my progression.

I will offer one more thought on the issue. Although neurologists are comfortable with removing spinal fluid for testing via a lumbar puncture, some neurologists, including mine, are less comfortable with administering treatments via a lumbar puncture. My neurologist recruited a local oncologist, who uses intrathecal methotrexate as a cancer treatment for some of his patients. My neurologist is still "in charge" of this treatment process, and the oncologist is functioning primarily as a high-priced medical technician (my insurance is covering all of this). So, if your neurologist's only objection is that he or she, personally, is uncomfortable injecting methotrexate this way, challenge him/her to help you find a local oncologist to become part of the team.

You mentioned the low cost of methotrexate. The bill for each of my infusions (one every eight weeks) is roughly $800. This consists of $150 for the office visit with the oncologist, and approximately $650 for the infusion itself. The cost of the drug? Seven dollars.

Thanks Marc for always keeping us informed. Interestingly, my neurologist recently prescribed methotrexate for my SPMS but it is taken orally (8.5 mg once a week). He also put me on a daily dose of folic acid to combat side effects. No noticeable changes but it's only been 3 weeks. I see him in a couple weeks and will bring print outs of the links you provided.

Hi Marc,I am a PhD student in Italy and I am working on social media topic regarding MS patients.Mainly I work on the ideas that patients exchange regarding their treatment and medicines improvement.

I would like to ask if there is any opportunity of cooperation. It would be really appreciated . My thesis focus is on improving MS patient's situtation by using social media. I need to know more people and use their ideas.Thanks

this is my email : fmoshtari@luiss.itplease let me know if we can work together.

Marc, If I had PPMS, I would probably try all these pharmaceutical approaches. I so appreciate hearing about what you are trying. I was treated by Dr. Scott Rosa last February with his atlas orthogonal device non invasively and had some really good results even though in the SPMS stage:I was having eyesight issues where I had kalidescope vision and could not drive. After the adjustment, my eyesight came back and I can drive again. My pre adjustment scans showed scoliosis in my neck with 4 points of blockage in my CSF flow...my atlas disk was diagonal and the C2 was rotated. The adjustment corrected the scoliosis, position of the atlas and my C2 was rotated less than 1%. Besides my eyesight being fixed, I have gotten most of my feeling back in my abdomen and fingers. Having said this, I have been negatively affected in my lumbar region. My right leg feels a couple of inches shorter(I am sure it is more like 1 inch) and my walking is much more challenged. It seems the correction in my neck has created scoliosis in my lumbar region. I don't want to give up my eyesight...but I sure wish there wasn't a trade-off.

just wanted to thank you for your wonderful articles you have given me some understanding of what is going on with me please continue to post as much as you can I think I have the same or simlar MS as you relatively Low scarring and yet I have lost the use of my legsI am hoping that I can show my neurologist your blog sometimes I think they don't know what to do with me is quick as possible in an out of that office even though I believe he's a good guy he doesn't know what to do with me.......

vague hope for us ppmsers , i wish there was a sure thing to stop my progression , i am getting weaker and can only use 11/2 of my body , 2xs for angioplasty , at least i have warm legs now , i use to be cold as ice , i wish anyone who tries this treatment the best of luck , i have 2 sons and im very weak at this point so experimental therapys are ut of the question , i am just trying my best to love so i can see my sons go to hischool ...thanks

Unfortunately, PPMS is a very difficult disease for both patients and researchers. Of course, it's worse for patients. I would recommend, though, at least discussing the possibility of intrathecal methotrexate treatment with your neurologist. The treatment is hardly experimental, as my neuro has used it successfully on hundreds of patients. Certainly, there are a fair number of nonresponders, but he has seen at least stability in quite a few of the progressive MS patients in which he has injected methotrexate intrathecally. Considering the complete lack of any other treatment that has shown any type of efficacy whatsoever for PPMS, the fact that intrathecal methotrexate has shown any benefit at all is reason to pursue the treatment. I wish you the best…

just wanted to thank you for your wonderful articles you have given me some understanding of what is going on with me please continue to post as much as you can I think I have the same or simlar MS as you relatively Low scarring and yet I have lost the use of my legsI am hoping that I can show my neurologist your blog sometimes I think they don't know what to do with me is quick as possible in an out of that office even though I believe he's a good guy he doesn't know what to do with me.......

In August, I will have my 3rd treatment. So far, i see no slowing, in fact ,maybe slight worsening of MS symptoms. Anyone else have this experience? Should I have the 3rd treatment, or just figure it doesn't help me? I have SPPMS.

It's probably too soon for you to judge the effectiveness of the treatment. Personally, I would give it four or five treatments before making any judgments, but this is certainly something you should discuss with your doctor.

I don't get it! My first symptoms gave me a Neuro dx of SPMS. I never had RRMS or PPMS. I rapidly went downhill from a weak arm to being bed bound, i.e. no walking, numb legs and a useless arm, with 50% use of the good arm within 5 years. I'm about ready for pasture - barring a miracle. Can't even prop myself up in bed. It sucks! Shingles and kidney stones are my visitors. I saw that Meredith Viera"s hubby with SPMS is going in for stem cell therapy (his own cells).

If you never had any relapses or remissions, then by definition you should have been diagnosed as PPMS. Secondary progressive multiple sclerosis is the stage that comes after relapsing remitting MS. That's why it's called secondary progressive. If you started out with progressive disability, then you would have PPMS.

I'm interested to find out more about Meredith Vieira's husband's treatment. Stem cells provide hope for all of us.

PS, your neuro may have given you a diagnosis of SPMS so that your insurance company would approve some treatments. There are approved treatments for SPMS, but none for PPMS. It's fairly common for neuros to use this "trick" so that they can at least try to treat their patients…

I have had ccsvi, and my own stem cells implanted, naltrexone, ampyra (thinking maybe I should try again since my walking is so much worse now. I pulse with prednisone (2-3 times per year) always bad around xmas. Not sure what is left - any brain waves.

I've used methotrexate for 20+ years for Crohn's disease (lucky me, I also have secondary progressive MS.) Since I started taking it I have had NO Crohn's symptoms. Methotrexate gave me my life back (imagine hustling- with MS! LOL - to a bathroom to poop 5 times a day). I think methotrexate also significantly slowed the rate of my MS disability. Don't expect miracles, methotrexate works for some– not all IBD cases respond. I ingest mine orally once a week.

Methotrexate is a powerful drug if prescribed for cancer, I never had hair loss and very few side effects because a very small dose does the trick for Crohn's patients. Just wanted to encourage anyone whose neurologist suggests trying it out. If your doctor suggests it, you may be like me and it could help.

I really love this idea of the intrathecal methotrexate. I've been in the medical field for over 30 years. I was Dx'd with MS in May of 2000. I did Avonex & Copaxone but I had issues with both because of a skin disorder. So I went without treatment until 2007, with the exception of doing oral steroids once or twice. I was awaiting on the oral med clinical trials to start but that didn't work out. I ended up going on Novantrone. Little did I know that it would put me out of the arena for ever doing a clinical trial ever again. I stopped the Novantrone after getting bacterial meningitis, then eventually I went on IVIG (Intravenous Immunoglobulin).

I've been on IVIG since either 2009 or 2010. My current Neuro & I decided to try tecfidera & I did my homework on it beforehand & also made sure I could still take the IVIG along with it. I ended up with the worst flare I'd ever had, my Dr moved me up the scale to SPMS. In May 2016 I had a flare that I thought wasn't near as bad but I lost muscle function. He's been on my case about being on a DMD but all of them have risk factors that I'm not willing to risk due to all the other health issues. I know it's because he wants me off the IVIG because there's no kickback for him. I was thinking about the methotrexate but I didn't know about the intrathecal option until I read your article. I'm not sure if it would be an option for me or not because I have rods & screws where they would normally do an LP. I think I'm going to bring it up at my next visit with him anyway just to see what he says.

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Regretfully, due to the high volume of e-mail received and the realities of living with progressive MS, I'll no longer be able to respond to all e-mails sent. I do read each note, and will do my best to answer as many messages as I can.

About Me

I'm Marc, a 53-year-old male, living in New York City with my lovely and wonderful wife Karen. Diagnosed with Primary Progressive Multiple Sclerosis in March of 2003, I now require a wheelchair to get around the city. I like to drive the wheelchair at full speed, thus the moniker "Wheelchair Kamikaze". I've managed to rig a camera to my chair, so I'm able to take videos and still photos from the unique vantage point of a wheelchair, which I intend to post here.
Before getting sick, I was the Director of DVD Production for one of the major international music companies. Yes, I was once a member of the Evil Empire...
Prior to my enlistment in the Evil Empire, I worked as a video producer and editor.
I grew up in New York City, and spent the 1980s in Boston (college and postcollege rock 'n roll craziness). During the 1990s, I lived in South Florida, until I woke up one morning and realized I was living in South Florida, came to my senses, and moved back to New York.
I hope you like my blog...